Characterizations of myosin essential light chain's N-terminal truncation mutant Δ43 in transgenic mouse papillary muscles by using tension transients in response to sinusoidal length alterations

Li Wang, Priya Muthu, Danuta Szczesna-Cordary, Masataka Kawai

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Cross-bridge kinetics were studied at 20 C in cardiac muscle strips from transgenic (Tg) mice expressing N-terminal 43 amino acid truncation mutation (Δ43) of myosin essential light chain (ELC), and the results were compared to those from Tg-wild type (WT) mice. Sinusoidal length changes were applied to activated skinned papillary muscle strips to induce tension transients, from which two exponential processes were deduced to characterize the cross-bridge kinetics. Their two rate constants were studied as functions of ATP, phosphate (Pi), ADP, and Ca2+ concentrations to characterize elementary steps of the cross-bridge cycle consisting of six states. Our results demonstrate for the first time that the cross-bridge kinetics of Δ43 are accelerated owing to an acceleration of the rate constant k 2 of the cross-bridge detachment step, and that the number of strongly attached cross-bridges are decreased because of a reduction of the equilibrium constant K 4 of the force generation step. The isometric tension and stiffness of Δ43 are diminished compared to WT, but the force per cross-bridge is not changed. Stiffness measurement during rigor induction demonstrates a reduction in the stiffness in Δ43, indicating that the N-terminal extension of ELC forms an extra linkage between the myosin cross-bridge and actin. The tension-pCa study demonstrates that there is no Ca2+ sensitivity change with Δ43, but the cooperativity is diminished. These results demonstrate the importance of the N-terminal extension of ELC in maintaining the myosin motor function during force generation and optimal cardiac performance.

Original languageEnglish (US)
Pages (from-to)93-105
Number of pages13
JournalJournal of Muscle Research and Cell Motility
Volume34
Issue number2
DOIs
StatePublished - May 2013

Keywords

  • Cardiac muscle
  • Cardiomyopathy
  • Cross-bridge cycle
  • Cross-bridge kinetics
  • Elementary steps
  • Muscle mechanics
  • Rate constants
  • Sinusoidal analysis
  • Tension transients

ASJC Scopus subject areas

  • Physiology
  • Cell Biology
  • Biochemistry

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